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Article ; Online: Body Image and High-Risk Weight and Shape Control Behaviors Among Transgender and Nonbinary Young Adults: The Role of Sexual Assault.

Eisenstadt, Benjamin E / Murchison, Gabriel R / Soulliard, Zachary A / Gordon, Allegra R

2023 Volume 10, Issue 8, Page(s) 586–594

Abstract: Purpose: ...

Abstract	Purpose:
MeSH term(s)	Humans ; Male ; Female ; Young Adult ; Gender Identity ; Transgender Persons ; Body Image ; Cross-Sectional Studies ; Sex Offenses ; Body Weight
Language	English
Publishing date	2023-07-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2727303-9
ISSN	2325-8306 ; 2325-8292
ISSN (online)	2325-8306
ISSN	2325-8292
DOI	10.1089/lgbt.2022.0324
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Peri-ictal activation of dorsomedial dorsal raphe serotonin neurons reduces mortality associated with maximal electroshock seizures.

Petrucci, Alexandra N / Jones, Allysa R / Kreitlow, Benjamin L / Buchanan, Gordon F

Brain communications

2024 Volume 6, Issue 2, Page(s) fcae052

Abstract: Over one-third of patients with epilepsy will develop refractory epilepsy and continue to experience seizures despite medical treatment. These patients are at the greatest risk for sudden unexpected death in epilepsy. The precise mechanisms underlying ... ...

Abstract	Over one-third of patients with epilepsy will develop refractory epilepsy and continue to experience seizures despite medical treatment. These patients are at the greatest risk for sudden unexpected death in epilepsy. The precise mechanisms underlying sudden unexpected death in epilepsy are unknown, but cardiorespiratory dysfunction and arousal impairment have been implicated. Substantial circumstantial evidence suggests serotonin is relevant to sudden unexpected death in epilepsy as it modulates sleep/wake regulation, breathing and arousal. The dorsal raphe nucleus is a major serotonergic center and a component of the ascending arousal system. Seizures disrupt the firing of dorsal raphe neurons, which may contribute to reduced responsiveness. However, the relevance of the dorsal raphe nucleus and its subnuclei to sudden unexpected death in epilepsy remains unclear. The dorsomedial dorsal raphe may be a salient target due to its role in stress and its connections with structures implicated in sudden unexpected death in epilepsy. We hypothesized that optogenetic activation of dorsomedial dorsal raphe serotonin neurons in
Language	English
Publishing date	2024-03-14
Publishing country	England
Document type	Journal Article
ISSN	2632-1297
ISSN (online)	2632-1297
DOI	10.1093/braincomms/fcae052
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Article ; Online: Accurate Prediction of Transcriptional Activity of Single Missense Variants in HIV Tat with Deep Learning.

Derbel, Houssemeddine / Giacoletto, Christopher J / Benjamin, Ronald / Chen, Gordon / Schiller, Martin R / Liu, Qian

International journal of molecular sciences

2023 Volume 24, Issue 7

Abstract: Tat is an essential gene for increasing the transcription of all HIV genes, and affects HIV replication, HIV exit from latency, and AIDS progression. The Tat gene frequently mutates in vivo and produces variants with diverse activities, contributing to ... ...

Abstract	Tat is an essential gene for increasing the transcription of all HIV genes, and affects HIV replication, HIV exit from latency, and AIDS progression. The Tat gene frequently mutates in vivo and produces variants with diverse activities, contributing to HIV viral heterogeneity as well as drug-resistant clones. Thus, identifying the transcriptional activities of Tat variants will help to better understand AIDS pathology and treatment. We recently reported the missense mutation landscape of all single amino acid Tat variants. In these experiments, a fraction of double missense alleles exhibited intragenic epistasis. However, it is too time-consuming and costly to determine the effect of the variants for all double mutant alleles through experiments. Therefore, we propose a combined GigaAssay/deep learning approach. As a first step to determine activity landscapes for complex variants, we evaluated a deep learning framework using previously reported GigaAssay experiments to predict how transcription activity is affected by Tat variants with single missense substitutions. Our approach achieved a 0.94 Pearson correlation coefficient when comparing the predicted to experimental activities. This hybrid approach can be extensible to more complex Tat alleles for a better understanding of the genetic control of HIV genome transcription.
MeSH term(s)	Humans ; tat Gene Products, Human Immunodeficiency Virus/genetics ; tat Gene Products, Human Immunodeficiency Virus/metabolism ; Transcriptional Activation ; Mutation, Missense ; Acquired Immunodeficiency Syndrome ; Deep Learning ; Transcription, Genetic
Chemical Substances	tat Gene Products, Human Immunodeficiency Virus
Language	English
Publishing date	2023-03-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24076138
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Article ; Online: Partial Repetition Costs are Reduced but not Eliminated with Practice.

Fournier, Lisa R / Richardson, Benjamin P / Logan, Gordon D

Journal of cognition

2022 Volume 5, Issue 1, Page(s) 37

Abstract: Often, we depart from an intended course of events to react to sudden situational demands (an intervening event) before resuming the originally planned action. Executing an action to an intervening event can be delayed if the features of this action ... ...

Abstract	Often, we depart from an intended course of events to react to sudden situational demands (an intervening event) before resuming the originally planned action. Executing an action to an intervening event can be delayed if the features of this action plan
Language	English
Publishing date	2022-06-23
Publishing country	England
Document type	Journal Article
ISSN	2514-4820
ISSN (online)	2514-4820
DOI	10.5334/joc.230
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Article: Therapeutic Drug Monitoring of Infliximab in Acute Severe Ulcerative Colitis.

Gordon, Benjamin L / Battat, Robert

Journal of clinical medicine

2023 Volume 12, Issue 10

Abstract: Therapeutic drug monitoring (TDM) is a useful strategy in ulcerative colitis (UC). Nearly a quarter of UC patients will experience acute severe UC (ASUC) in their lifetime, including 30% who will fail first-line corticosteroid therapy. Steroid-refractory ...

Abstract	Therapeutic drug monitoring (TDM) is a useful strategy in ulcerative colitis (UC). Nearly a quarter of UC patients will experience acute severe UC (ASUC) in their lifetime, including 30% who will fail first-line corticosteroid therapy. Steroid-refractory ASUC patients require salvage therapy with infliximab, cyclosporine, or colectomy. Fewer data are available for the use of TDM of infliximab in ASUC. The pharmacokinetics of ASUC make TDM in this population more complex. High inflammatory burden is associated with increased infliximab clearance, which is associated with lower infliximab drug concentrations. Observational data support the association between increased serum infliximab concentrations, lower clearance, and favorable clinical and endoscopic outcomes, as well as decreased rates of colectomy. Data regarding the benefit of accelerated or intensified dosing strategies of infliximab-as well as target drug concentration thresholds-in ASUC patients remain more equivocal, though limited by their observational nature. Studies are underway to further evaluate optimal dosing and TDM targets in this population. This review examines the evidence for TDM in patients with ASUC, with a focus on infliximab.
Language	English
Publishing date	2023-05-10
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm12103378
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Article ; Online: Accurate Prediction of Transcriptional Activity of Single Missense Variants in HIV Tat with Deep Learning

Houssemeddine Derbel / Christopher J. Giacoletto / Ronald Benjamin / Gordon Chen / Martin R. Schiller / Qian Liu

International Journal of Molecular Sciences, Vol 24, Iss 6138, p

2023 Volume 6138

Abstract	Tat is an essential gene for increasing the transcription of all HIV genes, and affects HIV replication, HIV exit from latency, and AIDS progression. The Tat gene frequently mutates in vivo and produces variants with diverse activities, contributing to HIV viral heterogeneity as well as drug-resistant clones. Thus, identifying the transcriptional activities of Tat variants will help to better understand AIDS pathology and treatment. We recently reported the missense mutation landscape of all single amino acid Tat variants. In these experiments, a fraction of double missense alleles exhibited intragenic epistasis. However, it is too time-consuming and costly to determine the effect of the variants for all double mutant alleles through experiments. Therefore, we propose a combined GigaAssay/deep learning approach. As a first step to determine activity landscapes for complex variants, we evaluated a deep learning framework using previously reported GigaAssay experiments to predict how transcription activity is affected by Tat variants with single missense substitutions. Our approach achieved a 0.94 Pearson correlation coefficient when comparing the predicted to experimental activities. This hybrid approach can be extensible to more complex Tat alleles for a better understanding of the genetic control of HIV genome transcription.
Keywords	variant effect ; deep learning ; HIV ; tat protein ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	572
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Probing C-I bond fission in the UV photochemistry of 2-iodothiophene with core-to-valence transient absorption spectroscopy.

Toulson, Benjamin W / Hait, Diptarka / Faccialà, Davide / Neumark, Daniel M / Leone, Stephen R / Head-Gordon, Martin / Gessner, Oliver

The Journal of chemical physics

2023 Volume 159, Issue 3

Abstract: The UV photochemistry of small heteroaromatic molecules serves as a testbed for understanding fundamental photo-induced chemical transformations in moderately complex compounds, including isomerization, ring-opening, and molecular dissociation. Here, a ... ...

Abstract	The UV photochemistry of small heteroaromatic molecules serves as a testbed for understanding fundamental photo-induced chemical transformations in moderately complex compounds, including isomerization, ring-opening, and molecular dissociation. Here, a combined experimental-theoretical study of 268 nm UV light-induced dynamics in 2-iodothiophene (C4H3IS) is performed. The dynamics are experimentally monitored with a femtosecond extreme ultraviolet (XUV) probe that measures iodine N-edge 4d core-to-valence transitions. Experiments are complemented by density functional theory calculations of both the pump-pulse induced valence excitations and the XUV probe-induced core-to-valence transitions. Possible intramolecular relaxation dynamics are investigated by ab initio molecular dynamics simulations. Gradual absorption changes up to ∼0.5 to 1 ps after excitation are observed for both the parent molecular species and emerging iodine fragments, with the latter appearing with a characteristic rise time of 160 ± 30 fs. Comparison of spectral intensities and energies with the calculations identifies an iodine dissociation pathway initiated by a predominant π → π* excitation. In contrast, initial excitation to a nearby n⟂ → σ* state appears unlikely based on a significantly smaller oscillator strength and the absence of any corresponding XUV absorption signatures. Excitation to the π → π* state is followed by contraction of the C-I bond, enabling a nonadiabatic transition to a dissociative π→σC-I* state. For the subsequent fragmentation, a relatively narrow bond-length region along the C-I stretch coordinate between 230 and 280 pm is identified, where the transition between the parent molecule and the thienyl radical + iodine atom products becomes prominent in the XUV spectrum due to rapid localization of two singly occupied molecular orbitals on the two fragments.
Language	English
Publishing date	2023-07-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	3113-6
ISSN	1089-7690 ; 0021-9606
ISSN (online)	1089-7690
ISSN	0021-9606
DOI	10.1063/5.0151629
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Article ; Online: Differences in management approaches for lupus nephritis within the UK.

Ibrahim, Sara T / Edwards, Christopher J / Ehrenstein, Michael R / Griffiths, Bridget / Gordon, Caroline / Hewins, Peter / Jayne, David / Lightstone, Liz / McLaren, Zoe / Rhodes, Benjamin / Vital, Edward M / Reynolds, John A

Rheumatology advances in practice

2024 Volume 8, Issue 1, Page(s) rkae017

Abstract: Objectives: Outcomes of therapy for LN are often suboptimal. Guidelines offer varied options for treatment of LN and treatment strategies may differ between clinicians and regions. We aimed to assess variations in the usual practice of UK physicians who ...

Abstract	Objectives: Outcomes of therapy for LN are often suboptimal. Guidelines offer varied options for treatment of LN and treatment strategies may differ between clinicians and regions. We aimed to assess variations in the usual practice of UK physicians who treat LN. Methods: We conducted an online survey of simulated LN cases for UK rheumatologists and nephrologists to identify treatment preferences for class IV and class V LN. Results: Of 77 respondents, 48 (62.3%) were rheumatologists and 29 (37.7%) were nephrologists. A total of 37 (48.0%) reported having a joint clinic between nephrologists and rheumatologists, 54 (70.0%) reported having a multidisciplinary team meeting for LN and 26 (33.7%) reported having a specialized lupus nurse. Of the respondents, 58 (75%) reported arranging a renal biopsy before starting the treatment. A total of 20 (69%) of the nephrologists, but only 13 (27%) rheumatologists, reported having a formal departmental protocol for treating patients with LN ( Conclusion: There was variation in the use of protocols, specialist clinic service provision, biopsies and primary and secondary treatment choices for LN reported by nephrologists and rheumatologists in the UK.
Language	English
Publishing date	2024-02-09
Publishing country	England
Document type	Journal Article
ISSN	2514-1775
ISSN (online)	2514-1775
DOI	10.1093/rap/rkae017
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Article ; Online: Genomic Loss and Epigenetic Silencing of the FOSL1 Tumor Suppressor Gene in Radiation-induced Neoplastic Transformation of Human CGL1 Cells Alters the Tumorigenic Phenotype In Vitro and In Vivo.

Pirkkanen, Jake / Tharmalingam, Sujeenthar / Thome, Christopher / Sinex, Helen Chin / Benjamin, Laura V / Losch, Adam C / Borgmann, Anthony J / Dhaemers, Ryan M / Gordon, Christopher / Boreham, Douglas R / Mendonca, Marc S

Radiation research

2023 Volume 200, Issue 1, Page(s) 48–64

Abstract: The CGL1 human hybrid cell system has been utilized for many decades as an excellent cellular tool for investigating neoplastic transformation. Substantial work has been done previously implicating genetic factors related to chromosome 11 to the ... ...

Abstract	The CGL1 human hybrid cell system has been utilized for many decades as an excellent cellular tool for investigating neoplastic transformation. Substantial work has been done previously implicating genetic factors related to chromosome 11 to the alteration of tumorigenic phenotype in CGL1 cells. This includes candidate tumor suppressor gene FOSL1, a member of the AP-1 transcription factor complex which encodes for protein FRA1. Here we present novel evidence supporting the role of FOSL1 in the suppression of tumorigenicity in segregants of the CGL1 system. Gamma-induced mutant (GIM) and control (CON) cells were isolated from 7 Gy gamma-irradiated CGL1s. Western, Southern and Northern blot analysis were utilized to assess FOSL1/FRA1 expression as well as methylation studies. GIMs were transfected to re-express FRA1 and in vivo tumorigenicity studies were conducted. Global transcriptomic microarray and RT-qPCR analysis were used to further characterize these unique cell segregants. GIMs were found to be tumorigenic in vivo when injected into nude mice whereas CON cells were not. GIMs show loss of Fosl/FRA1 expression as confirmed by Western blot. Southern and Northern blot analysis further reveals that FRA1 reduction in tumorigenic CGL1 segregants is likely due to transcriptional suppression. Results suggest that radiation-induced neoplastic transformation of CGL1 is in part due to silencing of the FOSL1 tumor suppressor gene promoter by methylation. The radiation-induced tumorigenic GIMs transfected to re-express FRA1 resulted in suppression of subcutaneous tumor growth in nude mice in vivo. Global microarray analysis and RT-qPCR validation elucidated several hundred differentially expressed genes. Downstream analysis reveals a significant number of altered pathways and enriched Gene Ontology terms genes related to cellular adhesion, proliferation, and migration. Together these findings provide strong evidence that FRA1 is a tumor suppressor gene deleted and epigenetically silenced after ionizing radiation-induced neoplastic transformation in the CGL1 human hybrid cell system.
MeSH term(s)	Animals ; Mice ; Humans ; Mice, Nude ; Cell Transformation, Neoplastic/genetics ; HeLa Cells ; Genes, Tumor Suppressor ; Carcinogenesis/genetics ; Neoplasms, Radiation-Induced/pathology ; Phenotype ; Genomics ; Epigenesis, Genetic ; Gene Expression Regulation, Neoplastic
Language	English
Publishing date	2023-05-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80322-4
ISSN	1938-5404 ; 0033-7587
ISSN (online)	1938-5404
ISSN	0033-7587
DOI	10.1667/RADE-22-00216.1
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Article ; Online: Improved Productivity with Multilaser Rotary Powder Bed Fusion Additive Manufacturing.

Wang, Peter / Robertson, Gordon / Gibson, Brian T / Fancher, Chris M / Reynolds, Jay / Borish, Michael / Cruz, Jesus R / Chesser, Phillip / Stump, Benjamin / Jackson, Amiee / MacDonald, Eric

3D printing and additive manufacturing

2024 Volume 11, Issue 1, Page(s) 231–241

Abstract: Laser powder bed fusion (LPBF) enables the fabrication of intricate, geometrically complex structures with a sufficiently fine surface finish for many engineering applications with a diversity of available feedstock metals. However, the production rate ... ...

Abstract	Laser powder bed fusion (LPBF) enables the fabrication of intricate, geometrically complex structures with a sufficiently fine surface finish for many engineering applications with a diversity of available feedstock metals. However, the production rate of LPBF systems is not well suited for mass production in comparison to traditional manufacturing methods. LPBF systems measure their deposition rates in 100's of grams per hour, while other processes measure in kilograms per hour or even in the case of processes such as forming, stamping, and casting, 100's of kilograms per hour. To be widely adopted in industry for mass production, LPBF requires a new scalable architecture that enables many orders of magnitude improvement in deposition rate, while maintaining the geometry freedom of additive manufacturing. This article explores concepts that could achieve as much as four orders of magnitude increase in the production rate through the application of (1) rotary table kinematic arrangements; (2) a dramatic number of simultaneously operating lasers; (3) reductions of laser optic size; (4) improved scanning techniques; and (5) an optimization of toroidal build plate size. To theoretically demonstrate the possibilities of production improvements, a productivity analysis is proposed for synchronous reluctance motors with relevance to the electric vehicle industry, given the recent increase in the diversity of printable soft magnetic alloys. The analysis provides insights into the impact of the architecture and process parameters necessary to optimize rotary powder bed fusion for mass production.
Language	English
Publishing date	2024-02-15
Publishing country	United States
Document type	Journal Article
ISSN	2329-7670
ISSN (online)	2329-7670
DOI	10.1089/3dp.2022.0288
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